tbuckley/cabot-search huggingface dataset:
Rates of Medicare Enrollment Among Dialysis Patients After Implementation of Medicare Payment Reform and the Affordable Care Act Marketplace
Authors: Virginia Wang, Lindsay Zepel, Bradley G. Hammill, Abby Hoffman, Caroline E. Sloan, Matthew L. Maciejewski
Journal: JAMA Network Open (2022)

Importance Medicare finances health care for most US patients with end-stage kidney disease (ESKD), regardless of age. The 2011 Medicare prospective payment system (PPS) for dialysis reduced reimbursement for hemodialysis, and the 2014 Patient Protection and Affordable Care Act (ACA) Marketplace increased patient access to new private insurance options, potentially influencing organizations that provide health care, such as hospitals, nursing homes, and dialysis facilities, to adjust their payer mix away from Medicare sources. Objective To describe Medicare enrollment trends among patients with incident ESKD in 2006 to 2016. Design, Setting, and Participants This retrospective cohort study involved US patients aged 18 to 64 years who were not enrolled in Medicare at dialysis initiation in 2006 to 2016, with 1-year follow-up through 2017. Data analysis was conducted April 2021 to June 2022. Exposures The exposure of interest was a 3-category indicator of time, whether patients initiated dialysis before policies were enacted (2006-2010), in the first years of the Medicare ESKD PPS (2011-2013), or during the Medicare ESKD PPS and implementation of the ACA Marketplace (2014-2016). Main Outcomes and Measures Patient-level Medicare enrollment through the first year of dialysis. Logistic regression and Cox models were used to examine associations of time, patient characteristics, and Medicare enrollment, adjusting for patient demographic, clinical, and market-level characteristics. Results Of 335 157 patients aged 18 to 64 years with ESKD not actively enrolled in Medicare when they initiated dialysis in 2006 to 2016, the mean (SD) age was 49.9 (10.8) years, 198 164 (59.1%) were men, 188 290 (56.2%) were White, and 313 622 (93.6%) received in-center hemodialysis. New Medicare enrollment was higher in 2006 to 2010 (110 582 patients [73.1%]) than after the Medicare ESKD PPS and ACA Marketplace in 2014 to 2016 (55 382 patients [58.5%]). In adjusted analyses, declining Medicare enrollment was associated with implementation of 2011 Medicare ESKD PPS and 2014 ACA policies and was disproportionately lower among younger, racially minoritized, and ethnically Hispanic patients. Conclusions and Relevance There was declining Medicare enrollment among new dialysis patients associated with the 2011 Medicare ESKD PPS and 2014 ACA Marketplace that raise concerns about benefits and harms to patients and payers and continued disparities in kidney care. As the dialysis payer mix moves toward higher proportions of patients not covered by Medicare, it will be important to understand the implications for health care system and patient outcomes.
Nonoperative repair of complete transection of the common bile duct using single-operator cholangioscopy
Authors: Lidia Marti Romero, Carlos Boix Clemente, Gloria Alemany Perez, Vanesa Martinez Escapa
Journal: Endoscopy (2022)

A 79-year-old woman with recurrent biliary colic due to cholelithiasis that had been observed via both ultrasonography and magnetic resonance cholangiography came to the hospital for a scheduled cholecystectomy. During the laparoscopic cholecystectomy, the common bile duct was accidentally sectioned. A choledochocholedochostomy was carried out with placement of a juxta-anastomotic Jackson–Pratt drain. Following this, the patient had 300 mL/day drain output, along with a biliary leak.
SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages
Authors: Giovanny J. Martínez-Colón, Kalani Ratnasiri, Heping Chen, Sizun Jiang, Elizabeth Zanley, Arjun Rustagi, Renu Verma, Han Chen, Jason R. Andrews, Kirsten D. Mertz, Alexandar Tzankov, Dan Azagury, Jack Boyd, Garry P. Nolan, Christian M. Schürch, Matthias S. Matter, Catherine A. Blish, Tracey L. McLaughlin
Journal: Science Translational Medicine (2022)

Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet the underlying mechanism is unknown. To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of adipose tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled the response of adipose tissue to SARS-CoV-2 infection in vitro. In COVID-19 autopsy cases, we identified SARS-CoV-2 RNA in adipocytes with an associated inflammatory infiltrate. We identified two distinct cellular targets of infection: adipocytes and a subset of inflammatory adipose tissue-resident macrophages. Mature adipocytes were permissive to SARS-CoV-2 infection; although macrophages were abortively infected, SARS-CoV-2 initiated inflammatory responses within both the infected macrophages and bystander preadipocytes. These data suggest that SARS-CoV-2 infection of adipose tissue could contribute to COVID-19 severity through replication of virus within adipocytes and through induction of local and systemic inflammation driven by infection of adipose tissue-resident macrophages.
Fibrotic immune microenvironment remodeling mediates superior anti-tumor efficacy of a nano-PD-L1 trap in hepatocellular carcinoma
Authors: Xiaoyu Liu, Jingying Zhou, Haoran Wu, Shufen Chen, Lingyun Zhang, Wenshu Tang, Liang Duan, Ying Wang, Eleanor McCabe, Mengying Hu, Zhuo Yu, Hanzhuang Liu, Chung Hang Jonathan Choi, Joseph Jao-yiu Sung, Leaf Huang, Rihe Liu, Alfred Sze-lok Cheng
Journal: Molecular Therapy (2022)

The local microenvironment where tumors develop can shape cancer progression and therapeutic outcome. Emerging evidence demonstrate that the efficacy of immune-checkpoint blockade (ICB) is undermined by fibrotic tumor microenvironment (TME). The majority of hepatocellular carcinoma (HCC) develops in liver fibrosis, in which the stromal and immune components may form a barricade against immunotherapy. Here, we report that nanodelivery of a programmed death-ligand 1 (PD-L1) trap gene exerts superior efficacy in treating fibrosis-associated HCC when compared with the conventional monoclonal antibody (mAb). In two fibrosis-associated HCC models induced by carbon tetrachloride and a high-fat, high-carbohydrate diet, the PD-L1 trap induced significantly larger tumor regression than mAb with no evidence of toxicity. Mechanistic studies revealed that PD-L1 trap, but not mAb, consistently reduced the M2 macrophage proportion in the fibrotic liver microenvironment and promoted cytotoxic interferon gamma (IFNγ)
Detection of Atrial Fibrillation in a Large Population Using Wearable Devices: The Fitbit Heart Study
Authors: Steven A. Lubitz, Anthony Z. Faranesh, Caitlin Selvaggi, Steven J. Atlas, David D. McManus, Daniel E. Singer, Sherry Pagoto, Michael V. McConnell, Alexandros Pantelopoulos, Andrea S. Foulkes
Journal: Circulation (2022)

Morbidity from undiagnosed atrial fibrillation (AF) may be preventable with early detection. Many consumer wearables contain optical photoplethysmography (PPG) sensors to measure pulse rate. PPG-based software algorithms that detect irregular heart rhythms may identify undiagnosed AF in large populations using wearables, but minimizing false-positive detections is essential.We performed a prospective remote clinical trial to examine a novel PPG-based algorithm for detecting undiagnosed AF from a range of wrist-worn devices. Adults aged ≥22 years in the United States without AF, using compatible wearable Fitbit devices and Android or iOS smartphones, were included. PPG data were analyzed using a novel algorithm that examines overlapping 5-minute pulse windows (tachograms). Eligible participants with an irregular heart rhythm detection (IHRD), defined as 11 consecutive irregular tachograms, were invited to schedule a telehealth visit and were mailed a 1-week ambulatory ECG patch monitor. The primary outcome was the positive predictive value of the first IHRD during ECG patch monitoring for concurrent AF.A total of 455 699 participants enrolled (median age 47 years, 71% female, 73% White) between May 6 and October 1, 2020. IHRDs occurred for 4728 (1%) participants, and 2070 (4%) participants aged ≥65 years during a median of 122 (interquartile range, 110-134) days at risk for an IHRD. Among 1057 participants with an IHRD notification and subsequent analyzable ECG patch monitor, AF was present in 340 (32.2%). Of the 225 participants with another IHRD during ECG patch monitoring, 221 had concurrent AF on the ECG and 4 did not, resulting in an IHRD positive predictive value of 98.2% (95% CI, 95.5%-99.5%). For participants aged ≥65 years, the IHRD positive predictive value was 97.0% (95% CI, 91.4%-99.4%).A novel PPG software algorithm for wearable Fitbit devices exhibited a high positive predictive value for concurrent AF and identified participants likely to have AF on subsequent ECG patch monitoring. Wearable devices may facilitate identifying individuals with undiagnosed AF.URL: https://www.gov; Unique identifier: NCT04380415.
Thermoresponsive and Injectable Hydrogel for Tissue Agnostic Regeneration
Authors: Dax Calder, Ali Fathi, Farshad Oveissi, Simin Maleknia, Terence Abrams, Yiwei Wang, Joanneke Maitz, Kevin Hung‐Yueh Tsai, Peter Maitz, Wojtek Chrzanowski, Ivan Canoy, Vivek Ashoka Menon, Kenneth Lee, Benjamin J. Ahern, Natasha E. Lean, Dina M. Silva, Paul M. Young, Daniela Traini, Hui Xin Ong, Rasoul Seyed Mahmoud, Hossein Montazerian, Ali Khademhosseini, Fariba Dehghani
Journal: Advanced Healthcare Materials (2022)

Injectable hydrogels can support the body's innate healing capability by providing a temporary matrix for host cell ingrowth and neovascularization. The clinical adoption of current injectable systems remains low due to their cumbersome preparation requirements, device malfunction, product dislodgment during administration, and uncontrolled biological responses at the treatment site. To address these challenges, a fully synthetic and ready-to-use injectable biomaterial is engineered that forms an adhesive hydrogel that remains at the administration site regardless of defect anatomy. The product elicits a negligible local inflammatory response and fully resorbs into nontoxic components with minimal impact on internal organs. Preclinical animal studies confirm that the engineered hydrogel upregulates the regeneration of both soft and hard tissues by providing a temporary matrix to support host cell ingrowth and neovascularization. In a pilot clinical trial, the engineered hydrogel is successfully administered to a socket site post tooth extraction and forms adhesive hydrogel that stabilizes blood clot and supports soft and hard tissue regeneration. Accordingly, this injectable hydrogel exhibits high therapeutic potential and can be adopted to address multiple unmet needs in different clinical settings.
Enzymatic Nanosphere‐to‐Nanofiber Transition and Autophagy Inducer Release Promote Tumor Chemotherapy
Authors: Xiaotong Cheng, Tiantian Xia, Wenjun Zhan, Hai‐Dong Xu, Jiaoming Jiang, Xiaoyang Liu, Xianbao Sun, Fu‐Gen Wu, Gaolin Liang
Journal: Advanced Healthcare Materials (2022)

Abstract Chemotherapy has remained an effective and predominant cancer treatment for the past decades, but is hampered by its low response rate and severe systemic toxicity. Combination chemotherapies are proposed to address these issues, yet their therapeutic outcomes are still far from satisfactory. Thus, it is urgent to develop novel strategies to promote tumor chemosensitivity while reducing toxic side effects of chemotherapeutics. Herein, employing a rationally designed peptide conjugate Nap‐Phe‐Phe‐Lys(SA‐AZD8055)‐Tyr(H 2 PO 3 )‐OH ( Nap‐AZD‐Yp ), a novel approach of simultaneous intracellular nanofiber formation and autophagy inducer release is proposed for selectively sensitizing tumor to chemotherapy. Upon sequential catalyses of alkaline phosphatase and carboxylesterase, Nap‐AZD‐Yp undergoes nanosphere‐to‐nanofiber transition accompanied by autophagy inducer AZD8055 release in cancer cells. Cell experiments show enhanced endocytosis of anticancer drug doxorubicin and inhibition of cell migration due to the intracellular nanofiber formation. The released AZD8055 further activates excessive autophagy of cancer cells, sensitizing them to chemotherapy. Animal experiment results suggest Nap‐AZD‐Yp can significantly enhance the therapeutic effects of doxorubicin on tumors while mitigate its toxic adverse effects on normal tissues. It is anticipated that the “smart” concept in this work c be widely employed to develop novel combinational therapies for the treatment of cancers and other diseases in near future.
Modifiable risk factors and long term risk of type 2 diabetes among individuals with a history of gestational diabetes mellitus: prospective cohort study
Authors: Jiaxi Yang, Frank Qian, Jorge E Chavarro, Sylvia H Ley, Deirdre K Tobias, Edwina Yeung, Stefanie N Hinkle, Wei Bao, Mengying Li, Aiyi Liu, James L Mills, Qi Sun, Walter C Willett, Frank B Hu, Cuilin Zhang
Journal: BMJ (2022)

Abstract Objectives To evaluate the individual and combined associations of five modifiable risk factors with risk of type 2 diabetes among women with a history of gestational diabetes mellitus and examine whether these associations differ by obesity and genetic predisposition to type 2 diabetes. Design Prospective cohort study. Setting Nurses’ Health Study II, US. Participants 4275 women with a history of gestational diabetes mellitus, with repeated measurements of weight and lifestyle factors and followed up between 1991 and 2009. Main outcome measure Self-reported, clinically diagnosed type 2 diabetes. Five modifiable risk factors were assessed, including not being overweight or obese (body mass index &lt;25.0), high quality diet (top two fifths of the modified Alternate Healthy Eating Index), regular exercise (≥150 min/week of moderate intensity or ≥75 min/week of vigorous intensity), moderate alcohol consumption (5.0-14.9 g/day), and no current smoking. Genetic susceptibility for type 2 diabetes was characterised by a genetic risk score based on 59 single nucleotide polymorphisms associated with type 2 diabetes in a subset of participants (n=1372). Results Over a median 27.9 years of follow-up, 924 women developed type 2 diabetes. Compared with participants who did not have optimal levels of any of the risk factors for the development of type 2 diabetes, those who had optimal levels of all five factors had &gt;90% lower risk of the disorder. Hazard ratios of type 2 diabetes for those with one, two, three, four, and five optimal levels of modifiable factors compared with none was 0.94 (95% confidence interval 0.59 to 1.49), 0.61 (0.38 to 0.96), 0.32 (0.20 to 0.51), 0.15 (0.09 to 0.26), and 0.08 (0.03 to 0.23), respectively (P trend &lt;0.001). The inverse association of the number of optimal modifiable factors with risk of type 2 diabetes was seen even in participants who were overweight/obese or with higher genetic susceptibility (P trend &lt;0.001). Among women with body mass index ≥25 (n=2227), the hazard ratio for achieving optimal levels of all the other four risk factors was 0.40 (95% confidence interval 0.18 to 0.91). Among women with higher genetic susceptibility, the hazard ratio of developing type 2 diabetes for having four optimal factors was 0.11 (0.04 to 0.29); in the group with optimal levels of all five factors, no type 2 diabetes events were observed. Conclusions Among women with a history of gestational diabetes mellitus, each additional optimal modifiable factor was associated with an incrementally lower risk of type 2 diabetes. These associations were seen even among individuals who were overweight/obese or were at greater genetic susceptibility.
Mechanical Stability of Nano‐Coatings on Clinically Applicable Electrodes, Generated by Electrophoretic Deposition
Authors: Vaijayanthi Ramesh, Nadine Stratmann, Viktor Schaufler, Svilen D. Angelov, Ilona D. Nordhorn, Hans E. Heissler, Ricardo Martínez‐Hincapié, Viktor Čolić, Christoph Rehbock, Kerstin Schwabe, Uwe Karst, Joachim K. Krauss, Stephan Barcikowski
Journal: Advanced Healthcare Materials (2022)

The mechanical stability of implant coatings is crucial for medical approval and transfer to clinical applications. Here, electrophoretic deposition (EPD) is a versatile coating technique, previously shown to cause significant post-surgery impedance reduction of brain stimulation platinum electrodes. However, the mechanical stability of the resulting coating has been rarely systematically investigated. In this work, pulsed-DC EPD of laser-generated platinum nanoparticles (PtNPs) on Pt-based, 3D neural electrodes is performed and the in vitro mechanical stability is examined using agarose gel, adhesive tape, and ultrasonication-based stress tests. EPD-generated coatings are highly stable inside simulated brain environments represented by agarose gel tests as well as after in vivo stimulation experiments. Electrochemical stability of the NP-modified surfaces is tested via cyclic voltammetry and that multiple scans may improve coating stability could be verified, indicated by higher signal stability following highly invasive adhesive tape stress tests. The brain sections post neural stimulation in rats are analyzed via laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Measurements reveal higher levels of Pt near the region stimulated with coated electrodes, in comparison to uncoated controls. Even though local concentrations in the vicinity of the implanted electrode are elevated, the total Pt mass found is below systemic toxicologically relevant concentrations.
Influenza vaccine effectiveness against A(H3N2) during the delayed 2021/22 epidemic in Canada
Authors: Shinhye Kim, Erica SY Chuang, Suzana Sabaiduc, Romy Olsha, Samantha E Kaweski, Nathan Zelyas, Jonathan B Gubbay, Agatha N Jassem, Hugues Charest, Gaston De Serres, James A Dickinson, Danuta M Skowronski
Journal: Eurosurveillance (2022)

Influenza virus circulation virtually ceased in Canada during the COVID-19 pandemic, re-emerging with the relaxation of restrictions in spring 2022. Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network reports 2021/22 vaccine effectiveness of 36% (95% CI: -38 to 71) against late-season illness due to influenza A(H3N2) clade 3C.2a1b.2a.2 viruses, considered antigenically distinct from the 3C.2a1b.2a.1 vaccine strain. Findings reinforce the World Health Organization's decision to update the 2022/23 northern hemisphere vaccine to a more representative A(H3N2) clade 3C.2a1b.2a.2 strain.
Slow Protein Dynamics Elicits New Enzymatic Functions by Means of Epistatic Interactions
Authors: Maria-Agustina Rossi, Timothy Palzkill, Fabio C L Almeida, Alejandro J Vila
Journal: Molecular Biology and Evolution (2022)

Abstract Protein evolution depends on the adaptation of these molecules to different functional challenges. This occurs by tuning their biochemical, biophysical, and structural traits through the accumulation of mutations. While the role of protein dynamics in biochemistry is well recognized, there are limited examples providing experimental evidence of the optimization of protein dynamics during evolution. Here we report an NMR study of four variants of the CTX-M β-lactamases, in which the interplay of two mutations outside the active site enhances the activity against a cephalosporin substrate, ceftazidime. The crystal structures of these enzymes do not account for this activity enhancement. By using NMR, here we show that the combination of these two mutations increases the backbone dynamics in a slow timescale and the exposure to the solvent of an otherwise buried β-sheet. The two mutations located in this β-sheet trigger conformational changes in loops located at the opposite side of the active site. We postulate that the most active variant explores alternative conformations that enable binding of the more challenging substrate ceftazidime. The impact of the mutations in the dynamics is context-dependent, in line with the epistatic effect observed in the catalytic activity of the different variants. These results reveal the existence of a dynamic network in CTX-M β-lactamases that has been exploited in evolution to provide a net gain-of-function, highlighting the role of alternative conformations in protein evolution.
The Genomic Landscapes of Desert Birds Form over Multiple Time Scales
Authors: Kaiya Provost, Stephanie Yun Shue, Meghan Forcellati, Brian Tilston Smith
Journal: Molecular Biology and Evolution (2022)

Spatial models show that genetic differentiation between populations can be explained by factors ranging from geographic distance to environmental resistance across the landscape. However, genomes exhibit a landscape of differentiation, indicating that multiple processes may mediate divergence in different portions of the genome. We tested this idea by comparing alternative geographic predctors of differentiation in ten bird species that co-occur in Sonoran and Chihuahuan Deserts of North America. Using population-level genomic data, we described the genomic landscapes across species and modeled conditions that represented historical and contemporary mechanisms. The characteristics of genomic landscapes differed across species, influenced by varying levels of population structuring and admixture between deserts, and the best-fit models contrasted between the whole genome and partitions along the genome. Both historical and contemporary mechanisms were important in explaining genetic distance, but particularly past and current environments, suggesting that genomic evolution was modulated by climate and habitat There were also different best-ftit models across genomic partitions of the data, indicating that these regions capture different evolutionary histories. These results show that the genomic landscape of differentiation can be associated with alternative geographic factors operating on different portions of the genome, which reflect how heterogeneous patterns of genetic differentiation can evolve across species and genomes.
Announcing the Lancet Global Health Commission on medical oxygen security
Authors: Freddy Eric Kitutu, Ahmed Ehanur Rahman, Hamish Graham, Carina King, Shams El Arifeen, Freddie Ssengooba, Leith Greenslade, Zoë Mullan
Journal: The Lancet Global Health (2022)

Medical oxygen is an essential health treatment for both acute and chronic conditions across all age groups. Strong medical oxygen systems save lives. Therefore, adequate access to safe, affordable, and appropriate medical oxygen services is crucial for improving population health and meeting the Sustainable Development Goal targets. However, severely limited or unreliable oxygen services have been a persistent issue in many low-income and middle-income countries (LMICs), particularly among small health facilities serving poor, rural, and otherwise marginalised populations.